Title: Gemini nanoparticles as a co-delivery system for antigen – CpG oligodeoxynucleotide adjuvant combination

Authors: Ildiko Badea, Shawn Babiuk, Lorne Babiuk, Marianna Foldvari

Addresses: College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Thorvaldson Building, Room G22, Saskatoon, Saskatchewan, S7N 5C9, Canada. ' Canadian Food Inspection Agency, 1015 Arlington Street, Winnipeg, Manitoba, R3E 3M4, Canada; Department of Immunology, University of Manitoba, 471 Apotex Centre, 750 McDermot Avenue, Winnipeg, Manitoba R3E 0T5, Canada. ' University of Alberta, Third Floor University Hall, Edmonton, Alberta, T6G 2J9, Canada. ' School of Pharmacy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada

Abstract: Enhancement of antigen-specific immune responses could be achieved by co-delivery of antigens and adjuvants. CpG oligodeoxynucleotides (unmethylated cytosine-guanine tandems in a specific sequence; ODNs) increase innate and antigen-specific immune responses. Effective co-delivery approaches of CpG ODNs and antigens to antigen-presenting cells are needed to achieve more potent antigen-specific immune responses. We evaluated both cellular and humoural immune responses triggered by hen egg lysozyme (HEL), a model antigen, and CpG ODNs formulated in gemini surfactant and dioleoyl phosphatidylcholine-based nanoparticles as an intradermal and topical co-delivery system in a murine animal model. Overall, intradermal injection of HEL/CpG nanoparticles induced a more pronounced Th1 immune response compared with the HEL and HEL/CpG topical formulations, as evidenced by the shift in the Th2 response triggered by the antigen alone to a mixed Th1/Th2 immune response and increased the presence of interferon-gamma (IFN-γ) secreting cells in the spleen. However, in case of topical administration, the nanoparticle formulation of HEL produced enhanced immune response and immunomodulation even without the incorporation of CpG. The HEL-specific immune response and Th1 bias demonstrated the advantage of co-delivery of HEL/CpG ODNs by gemini nanoparticles intradermally, whereas, the adjuvant effect of the nanoparticle delivery system itself was more significant after topical treatment.

Keywords: gemini surfactant; gemini nanoparticles; vaccine delivery; topical delivery; intradermal delivery; CpG ODNs; hen egg lysozyme; HEL; immune response; Th1/Th2 immune response; immunomodulation; drug delivery; nanotechnology; antigens; adjuvants; oligodeoxynucleotides.

DOI: 10.1504/IJBNN.2010.034656

International Journal of Biomedical Nanoscience and Nanotechnology, 2010 Vol.1 No.2/3/4, pp.290 - 307

Published online: 13 Aug 2010 *

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